The motley group included men and women, old and young, in sweatshirts and three-piece suits, shod in socks and sandals, wingtips and heels. They were a kind of neuroscience dream team, more than 100 scientists gathered in a Bethesda, Md., hotel not to talk about their latest breakthroughs — there weren’t any yet — but to meet and get to know one another.
Eighteen months after President Obama launched an ambitious brain-research initiative, likened by some to the moonshot of the 1960s, federal officials are trying to create a new model for neuroscience research, one that emphasizes innovation and cooperation across specialties and institutions. To do that, they threw a two-day “kickoff” for scientists fortunate enough to have received the first funding slices of what probably will be a multibillion-dollar federal pie.
The “mixer” in Maryland was organized by the National Institutes of Health and the National Science Foundation, two of the agencies leading the sweeping scientific effort to develop a complete guide to the anatomy, activity and functioning of the human brain. The government’s scientists already had tossed out the playbook on how research usually is done — conservatively, competitively and narrowly — and had embraced the highest-risk, highest-reward research projects they could identify.
The first grants for the BRAIN Initiative, whose formal name is Brain Research Through Advancing Innovative Neurotechnologies, were awarded in September; the November mixer provided intellectual cross-pollination for the researchers involved. Now, as the new year starts, the hard, slow grind for answers to some of the most enduring mysteries of the human mind is getting underway.
The architects of the project, which could provide clues to ailments such as Alzheimer’s and schizophrenia, wait anxiously in the wings, hoping their efforts will help speed that process.
“This can’t be business as usual,” said one of those architects, Rockefeller University neurobiologist Cornelia Bargmann. “This is a new culture bridging physicists, engineers, biologists, chemists . . . with a big emphasis on showing new results and discoveries.”
The impetus for the brain-research effort, announced by Obama in April 2013, was a simple, staggering statistic: 1 in 4 families worldwide includes someone who suffers from a brain injury, disease or disorder, including psychiatric illnesses and developmental disorders, according to MIT’s McGovern Institute for Brain Research. In the United States, the economic burden for neurological problems is nearly a half-trillion dollars every year.
That formidable arithmetic fueled the belief that the initiative — and everything about it, from its goals to the scientists picked to pursue those goals — needed to be innovative.
Participants often compare their mission with the Human Genome Project, the massive, federally funded collaboration that mapped the order of organic compounds in human DNA. Those compounds are fundamental to the growth and development of all organisms in the same way that neurons are key to their functioning. But understanding the precise structure, organization and activity of human brain cells is massively more complex than unraveling human DNA.
There are approximately 86 billion neurons in our brain, and at a minimum those neurons contain 100 trillion synapses, or connections. Identifying synaptic connections is further complicated by the fact that while the genome is essentially fixed, the brain is changing constantly. Every thought, every emotion, every act we perform creates, redirects, strengthens or weakens neural connections.
Critics contend that the brain project is too Icarus-like in its intentions; its goals are too lofty and the price tag is too high and yet not high enough — too high because it would divert money from other science programs but not high enough because of the sheer enormity of the initiative. The Human Genome Project, which needed $2.7 billion to complete, was undertaken in the early 1990s, before extreme federal belt-tightening. Today, funding rates for research grants are at historic lows. Even so, NIH envisions a $4.8 billion outlay over a little more than a decade, with the largest portion of grant money going to NIH, the NSF and the Defense Advanced Research Projects Agency, or DARPA. The latest budget legislation approved by Congress, however, included only modest increases over the initial $110 million provided for the project.
“Many people are having a tough time keeping their labs afloat,” behavioral neuroscientist Bethany Brookshire wrote on her Scientific American blog. “All of this money? It may just be a stopgap to put the funding in neuroscience a little closer to where it’s been previously (to say nothing of the other disciplines forced to struggle on without their own acronymed initiatives).”
There is reason for optimism, however. Five federal agencies are involved, and at least eight private foundations and public companies, including Google and General Electric, have said they will kick in an additional $122 million for their own neuroscience projects. Other organizations — and countries — also are pitching in. Seattle’s Allen Institute for Brain Science, funded by Microsoft co-founder Paul G. Allen, helped lay the groundwork for the government’s brain-research effort, which also is working closely with the European Union’s Human Brain Project. Japan, Australia and Israel also are in the planning stages of their own national neuro projects, and China launched its program nearly a decade ago.
With a second round of funding to go out soon for the U.S. effort, the goals are both short- and long-term and include creating structural maps of the brain, linking neuron activity to human behavior and using new data to develop theories on how the healthy human brain works.
The only way to achieve these goals, neuroscientists say, is to develop new tools. So among the items on NIH’s wish list are lasers, radio waves and genetically modified viruses that would enable researchers to record wide swaths of brain activity.
When a committee chose the first group of research projects, there was essentially one criterion: “What are we willing to take a risk on?” said James O. Deshler, a deputy director at the NSF.
Ninety-four projects out of more than 600 made the cut. Among the principal investigators were electrical engineers, physicists and pharmacologists. Grants were given to a few usual suspects, big names such as MIT’s Robert Desimone, director of the McGovern Institute, but also to junior professors such as West Virginia University’s Julie Brefczynski-Lewis, who had a radical idea — a wearable PET scanner — and a plan for building it.
The members of this freshman class of researchers hail from 15 states and three countries, but asking them to collaborate before the ink was dry on their grants was like asking rival politicians to share campaign strategies. If there is any hope of understanding the human cerebrum in this lifetime, however, officials knew it was necessary.
Which is why on the first morning of the kickoff meeting, the NIH chaperons herded their charges together, pointed out the restrooms, suggested where to go for lunch and gave them a WiFi password no one was likely to forget: BRAIN.
Not surprisingly, man’s most defining organ is also the least understood. Although each 3-pound human brain is made up of close to 100 billion neurons, scientists do not know how many different kinds of human neurons exist. For the past six years, the Neuroscience Information Framework, a Web-based NIH inventory of neuroscience resources, has kept a running tab of neuron types. The number currently sits at 754 — and counting.
Even how scientists talk about the brain is fraught with obfuscation because there is no consistent, universally agreed-upon lexicon. Depending on a researcher’s subject matter, a term as basic as “cerebral cortex,” the brain’s outer covering of gray matter, can be defined in different ways — by its tissue layers, its neurons, its functions, etc. — which makes searching databases onerous and duplicating research inevitable.
The problem of a common lexicon is not even a recent one. In his 1915 textbook, “An Introduction to Neurology,” the University of Chicago’s Charles Judson Herrick wrote, “The terminology of the brain is in great confusion.”
Only one species has had the entirety of its brain connections, called a connectome, mapped. At one millimeter in length, the C. elegansroundworm has 302 neurons, harboring about 6,400 connections. It took scientists more than a decade to complete a map of its neural code, but that was in 1986, before automated brain sectioning and computer algorithm data analysis.
Mapping the human connectome, at least right now, seems almost beyond comprehension. In just a single cubic millimeter of human brain tissue — about the size of a grain of salt — there are 30,000 neurons and 50 million connections.
A true map of human brain function is not at all like the map of a human genome, according to Richard Kramer, a neurobiologist at the University of California at Berkeley and one of the initiative’s principal investigators. He said the landscape of the brain is more than just a series of neuronal highways marked by synaptic exits and entrances.
“The map we have is just a skeleton,” Kramer said. “It’s the personality of all the places at the ends of those exits that we don’t know about.”
Before the kickoff meeting formally began, Mriganka Sur, an MIT neuroscientist, introduced himself to Cornell University’s Chris Xu. Both work in the relatively new field of optogenetics, using lasers to track brain connections. And both have the kind of cross-disciplinary backgrounds NIH was seeking when it doled out its portion of the BRAIN Initiative’s fiscal pie.
Sur is an electrical engineer who became a biologist because he was fascinated with the brain as an information-processing device that runs on electricity. Xu’s degree is in applied and engineering physics with a focus on biomedical imaging and fiber optics.
A few hours later, lunchtime became a kind of meet-and-greet session for many of the investigators. That’s when Dean Foster Wong, a professor of radiology at Johns Hopkins University, ran into West Virginia’s Brefczynski-Lewis, an assistant professor of physiology and pharmacology.
“You’re the PET helmet woman!” Wong exclaimed, correctly identifying Brefczynski-Lewis’s project, which involves the creation of a portable positron emission tomography scan capable of imaging activity in deep brain structures as a person moves, talks or performs a task.
“We’re really PET researchers, and we study psychiatric disorders,” Wong continued, “and we’d love to work with you.”
Brefczynski-Lewis was not familiar with Wong’s research, but she certainly was game — and that is just what the NIH and NSF officials were counting on.
“We all know we need a system change, a flow of ideas across disciplines,” said William Newsome, a Stanford neurobiologist and one of the leaders of the initiative. “Make it more of a group enterprise where people get credit for collaborating.”
Not content with talking over lunch, Wong and Brefczynski-Lewis made a date for dinner that night. The West Virginia scientist told the Hopkins researcher about her previous work studying abnormal eye movements in schizophrenics. He told her about his research into dopamine receptors in schizophrenics. Suddenly Brefczynski-Lewis’s wearable PET scanner seemed to have found a new role in the investigation of a serious mental illness.
During a phone interview two weeks later, she paused for a second or two in mid-sentence, then laughed.
“He just sent me an e-mail as we were talking,” she said, referring to Wong. He wanted to know if she could provide him with a slide of her PET helmet for a talk he was scheduled to give.
She quickly e-mailed him back.
Of course she could.